Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women

BackgroundAlthough studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.MethodsA total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.ResultsIn premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.ConclusionIncreased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women

BackgroundAlthough studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.MethodsA total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.ResultsIn premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.ConclusionIncreased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry

Background@#There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis. @*Methods@#We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively. @*Results@#Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; p=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; p=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; p<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; p<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (p=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (p=0.023). @*Conclusion@#Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

Background@#Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes.Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. @*Methods@#We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. @*Results@#OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. @*Conclusion@#We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production.Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.

Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. METHODS: Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. RESULTS: Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. CONCLUSION: Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis

BACKGROUND: The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD. METHODS: We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as > or =50% diameter stenosis in at least one coronary artery. RESULTS: Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 micromol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028). CONCLUSION: Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.

Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. METHODS: To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. RESULTS: Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 microIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. CONCLUSION: The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Management of Non-alcoholic Fatty Liver Disease / 임상당뇨병

Non-alcoholic fatty liver disease (NAFLD) is a common condition that may progress to end-stage liver disease. Recently, it has been recognized as a hepatic manifestation of metabolic syndrome and an independent risk factor for cardiovascular disease. Therefore, managing this common disorder is becoming an important public health issue. The management of NAFLD is based on gradual weight loss through lifestyle modification. Reducing total calorie intake and carbohydrates in the diet is beneficial for NAFLD patients. Regular exercise reduces hepatic fat content independent of weight loss. However, such life style changes are known to be difficult to maintain in the long term for most patients. Despite the growing need for pharmacologic therapy, there is currently no effective agent for the treatment of NAFLD. Several large clinical trials have shown promising but inconsistent effects of pioglitazone and vitamin E in improving NAFLD. Trials with ursodeoxycholic acid or metformin have been disappointing.Recently, promising evidence has shown that incretin-based therapies may improve NAFLD. Larger clinical trials are required before a definite conclusion can be made.

The Impacts of Alcohol Consumption on Glucose Metabolism / 임상당뇨병

The relationship between alcohol consumption and carbohydrate metabolism is complex and is not fully understood. Alcohol not only increases oxidative stress during metabolism, but also inhibits both gluconeogenesis and glycogenolysis in liver. Thus, acute alcohol intake can lead to hypoglycemia, particularly when glycogen stores are depleted or when alcohol is taken without meals. In addition, carbohydrate-rich food taken together with alcohol exaggerates insulin secretion and can cause reactive hypoglycemia about 2 to 3 hours after the meal. It is well established that mild to moderate alcohol consumption (3 drinks/day) is associated with reduced cardiovascular mortality through improvements in insulin sensitivity, lipid profiles, and blood pressure. These beneficial effects of alcohol may also be responsible for a decreased incidence of type 2 diabetes mellitus (T2DM) and a reduced risk of coronary heart disease (CHD) in patients with T2DM. However, excessive alcohol consumption causes higher insulin resistance and increases the risk of T2DM, and even reverses the favorable effects of moderate alcohol intake on CHD.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.

Various Oscillation Patterns of Serum Fibroblast Growth Factor 21 Concentrations in Healthy Volunteers

BACKGROUND: Fibroblast growth factor 21 (FGF21) was originally identified as a paroxysm proliferator activated receptor-alpha target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers. METHODS: Blood samples were collected from five non-obese (body mass index [BMI] or =25 kg/m2) healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured. RESULTS: The serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P or =0.19 ng/mL). CONCLUSION: Various oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.

The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital

BACKGROUND: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD. METHODS: A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI < or =0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD. RESULTS: Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD. CONCLUSION: The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.

A Case of Familial Multiple Endocrine Neoplasia Type 1 with a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple tumors in the parathyroid gland, pancreatic islet, and pituitary gland. This condition is caused by mutations of MEN1, a tumor suppressor gene. Thus far, 565 different germline and somatic mutations of the MEN1 gene have been reported. Herein, we describe the case of a 23-year-old woman who suffered from a repetitive loss of consciousness. After workup, the patient was diagnosed with MEN1 with insulinoma, hyperparathyrodism due to parathyroid adenoma, and non-functioning pituitary microadenoma. She underwent a partial parathyroidectomy and distal pancreatectomy. Familial screening of MEN1 revealed that her brother had prolactinoma, hyperparathyroidism, pancreatic gastrinoma and non-functioning adrenal adenoma. Her father had hyperparathyroidism, pancreatic tumor, and adrenal adenoma. Upon genetic analysis of the MEN1 gene, a novel mutation in the MEN1 gene (exon 1, c.251del; p.Ser84LuefsX35) was detected in the patient, as well as her father and brother.

Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients / 당뇨병

BACKGROUND: Serum cystatin C level is a more sensitive marker of renal dysfunction than serum creatinine level. Serum cystatin C level was recently reported to predict the development of cardiovascular disease. This study was performed to evaluate whether the cystatin C level is associated with coronary artery disease (CAD), independent of diabetic nephropathy. METHODS: We conducted a case-control study to assess the relationship between serum cystatin C level and coronary artery disease in diabetic patients. Among 460 diabetic patients, 38 diabetic patients had CAD. The control group consisted of 38 diabetic patients who were matched to cases by age, sex, and presence/absence of diabetic nephropathy. Serum cystatin C level was measured in stored samples. RESULTS: Serum cystatin C level was significantly higher in patients with diabetic nephropathy, both in CAD and non-CAD patients. However, serum cystatin C level did not differ between CAD and non-CAD patients, regardless of diabetic nephropathy. CONCLUSION: Serum cystatin C level is a marker of renal dysfunction, but not coronary artery disease, in diabetic patients.

Adenine Nucleotide Translocator as a Regulator of Mitochondrial Function: Implication in the Pathogenesis of Metabolic Syndrome / 당뇨병

Mitochondria play key roles in energy production and intracellular reactive oxygen species (ROS) generation. Lines of evidence have shown that mitochondrial dysfunction contributes to the development of metabolic syndrome. The causes of mitochondrial dysfunction are complex, but overnutrition and sedentary living are among the best known causes of mitochondrial dysfunction. ATP synthesized in the mitochondria is exchanged for cytosolic ADP by adenine nucleotide translocator (ANT) to provide a continuous supply of ADP to mitochondria. We recently found that ANT function is essential for peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha)'s action on endothelial cells. PGC-1alpha is a transcriptional coactivator of nuclear receptors, playing an important role in fatty acid oxidation and mitochondrial biogenesis. Recent studies have shown that PGC-1alpha decreases intracellular ROS generation by increasing the expression of antioxidant genes. In our study, PGC-1alpha reduced cell apoptosis and ROS generation in endothelial cells by increasing ATP/ADP translocase activity of ANT and ANT1 expression. Here we review the role of ANT in maintaining proper mitochondrial function, and possible role of ANT dysfunction in the pathogenesis of metabolic syndrome.

Homocysteine as a Risk Factor for Development of Microalbuminuria in Type 2 Diabetes / 당뇨병

BACKGROUND: Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes. METHODS: A nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 +/- 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples. RESULTS: Baseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes. CONCLUSION: Hyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.

Efficacy and Safety of Cabergoline as First Line Treatment for Invasive Giant Prolactinoma

Although cabergoline is effective in the treatment of micro- and macro-prolactinoma, little is known about its efficacy in the treatment of invasive giant prolactinoma. We investigated the efficacy and safety of cabergoline in 10 male patients with invasive giant prolactinoma. Before treatment, mean serum prolactin level was 11,426 ng/mL (range, 1,450-33,200 ng/mL) and mean maximum tumor diameter was 51 mm (range, 40-77 mm). Three months after initiation of cabergoline treatment, serum prolactin concentrations decreased more than 97% in 9 patients; at last follow-up (mean treatment duration, 19 months), the mean decrease in serum prolactin concentrations was 98%, with 5 patients having normal serum prolactin levels. At first MRI follow-up (3-12 months after initiation of cabergoline), the mean reduction in tumor size was 85+/-4% (range, 57-98%). Cabergoline treatment for more than 12 months caused a greater reduction in tumor size compared to the treatment for less than 12 months (97+/-1% vs. 78+/-7%, P<0.05). These findings indicate that cabergoline treatment led to a significant and rapid reduction in serum prolactin concentrations and tumor size in patients with giant prolactinoma. Therefore, cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma.

Anti-GAD Antibody in Patients with Adult-Onset Diabetes in Korea / 당뇨병

BACKGROUND: It is well known that the clinical characteristics of diabetes mellitus in Korean people are different from those of Western people. The purpose of this study was to investigate the prevalence of the anti-GAD antibody (GADA) in a large number of Korean patients with adult-onset diabetes. METHODS: The GADA was measured by radioimmunoassay for 11,472 adult-onset diabetic patients who visited the Asan Medical Center from 1998 to 2007. According to the fasting C-peptide levels, we classified the patients into an insulin dependent diabetes mellitus group (IDDM; C-peptide or = 1.0 ng/mL). Other clinical and laboratory data were obtained from medical records. RESULTS: Among the 11,147 diabetic patients, 9,250 patients were classified as NIDDM, 922 patients were classified as IDDM and 975 patients excluded. Within the latter group 472 patients were to absolute insulin deficient (C-peptide or = 40 years of age; 3.8%). The GADA-positive NIDDM patients had lower C-peptide and BMI levels, and higher rates of typical diabetic symptoms and insulin treatment. CONCLUSION: The prevalence of GADA in Korean patients with IDDM and NIDDM was lower than that reported in Western populations. It is thus suggested that autoimmunity is a rarer cause of diabetes in Korean people. However, since over 10% of younger-onset NIDDM patients were positive for GADA, routine GADA measurement in such patients is recommended.

Nitric Oxide Increases Insulin Sensitivity in Skeletal Muscle by Improving Mitochondrial Function and Insulin Signaling / 당뇨병

BACKGROUND: Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function. METHODS: In Sprague-Dawley (SD) rats treated with SIN-1 for 4 weeks, insulin sensitivity was measured by a glucose clamp study. Triglyceride content and fatty acid oxidation were measured in the skeletal muscle. In addition, mitochondrial DNA content and mRNA expression of mitochondrial biogenesis markers were assessed by real-time polymerase chain reaction and expression of insulin receptor substrate (IRS)-1 and Akt were examined by Western blot analysis in skeletal muscle. In C2C12 cells, insulin sensitivity was measured by 2-deoxyglucose uptake and Western blot analysis was used to examine the expression of IRS-1 and Akt. RESULTS: SIN-1 improved insulin sensitivity in C2C12 cells and skeletal muscles of SD rats. In addition, SIN-1 decreased triglyceride content and increased fatty acid oxidation in skeletal muscle. Mitochondrial DNA contents and biogenesis in the skeletal muscle were increased by SIN-1 treatment. Moreover, SIN-1 increased the expression of phosphor-IRS-1 and phosphor-Akt in the skeletal muscle and muscle cells. CONCLUSION: Our results suggest that NO mediates glucose uptake in skeletal muscle both in vitro and in vivo by improving mitochondrial function and stimulating insulin signaling pathways.